We report the identification and cloning of a novel human gene, CXorf17, together with its mouse ortholog, orf34. The human and mouse transcripts were cloned from brain cDNA and encode deduced proteins of 1096 and 1091 amino acids, respectively. These proteins are 92% identical and 95% similar at the protein level. CXorf17 appears to be expressed at low levels and could be detected by RT-PCR in several adult and fetal human tissues. Analysis of the deduced amino acid sequence identified five putative transmembrane domains but no significant homology to previously described protein domains or sequence motifs. The CXorf17 protein has homology to two other non-annotated human proteins, C9orf10 and BC012177, the sequence similarity between them being strongest across two discrete domains of 250-270 amino acids in the N- and C-terminal parts of their sequences. We propose that these proteins belong to a previously undescribed family of putative transmembrane proteins. The identification of ESTs coding for similar proteins in other chordates but not lower eukaryotes suggests that these proteins may have first evolved during early chordate evolution. CXorf17 consists of 16 coding exons and maps to Xp11.22, approximately 14 kb telomeric to PRKWNK3 and 27 kb centromeric to KIAA1111. Its identification contributes to the annotation of expressed genes in the proximal part of the X chromosome.